Werkmeister J A, Roder J C, Curry C, Pross H F
Cell Immunol. 1983 Aug;80(1):172-86. doi: 10.1016/0008-8749(83)90104-1.
A number of different sugars were investigated for their effect on human and mouse natural killer cell (NK)-mediated cytolysis. From the pool of nonphosphorylated sugars, D-mannose, N-acetyl-D-glucosamine (NAcGlc), D-glucose, and, to a lesser extent, beta-gentiobiose were found to inhibit human NK cytolysis. Mouse NK activity against YAC-1 target cells was reduced consistently in the presence of D-mannose and NAcGlc only. The sugars, NAcGlc, D-glucose, and beta-gentiobiose, were specifically inhibitory against NK-mediated cytolysis with no inhibitory effects being observed against ADCC, monocyte-mediated cytolysis, or CTL activity. Pretreatment and washing at either the target or effector cell level as well as direct target binding assays using Percoll-purified NK cells indicated that at least NAcGlc and beta-gentiobiose function at the recognition stage of NK cytolysis. D-Mannose, which was the most effective nonphosphorylated sugar inhibitor, was capable of inhibiting all cell-mediated cytotoxic mechanisms tested (NK, ADCC, monocyte, and CTL) and its action did not appear to be solely due to an impairment in the recognition event. All the phosphorylated sugars caused significant inhibition of human and mouse NK-mediated cytolysis, although repeated analyses of sugar titration curves consistently showed mannose-6-phosphate (Man-6-P) to be the most effective inhibitor. Inhibition with the phosphorylated sugars was apparent against all cytotoxic mechanisms investigated. It is possible that these sugars may function as general metabolic inhibitors or may activate a common signal which negatively regulates cell-mediated cytotoxic mechanisms. Nevertheless, the relative degree of inhibition with the majority of these sugars (particularly Man-6-P) was greater against NK and ADCC activity than against monocyte and CTL activity. Furthermore, studies with selected well-characterized human and mouse NK-resistant target cells strongly indicated that these sugars, particularly Man-6-P, compete at an acceptor site responsible for the uptake of the NK lytic factor, which is independent of the recognition structure(s).
研究了多种不同糖类对人及小鼠自然杀伤细胞(NK)介导的细胞溶解作用的影响。在非磷酸化糖类中,发现D-甘露糖、N-乙酰-D-葡萄糖胺(NAcGlc)、D-葡萄糖,以及程度较轻的β-龙胆二糖可抑制人NK细胞溶解。仅在存在D-甘露糖和NAcGlc时,小鼠对YAC-1靶细胞的NK活性持续降低。糖类NAcGlc、D-葡萄糖和β-龙胆二糖对NK介导的细胞溶解具有特异性抑制作用,而对抗体依赖的细胞介导的细胞毒性作用(ADCC)、单核细胞介导的细胞溶解或细胞毒性T淋巴细胞(CTL)活性未观察到抑制作用。在靶细胞或效应细胞水平进行预处理和洗涤,以及使用Percoll纯化的NK细胞进行直接靶细胞结合试验表明,至少NAcGlc和β-龙胆二糖在NK细胞溶解的识别阶段起作用。D-甘露糖是最有效的非磷酸化糖类抑制剂,能够抑制所测试的所有细胞介导的细胞毒性机制(NK、ADCC、单核细胞和CTL),其作用似乎并非仅仅由于识别事件受损。所有磷酸化糖类均显著抑制人及小鼠NK介导的细胞溶解,尽管对糖滴定曲线的反复分析始终表明6-磷酸甘露糖(Man-6-P)是最有效的抑制剂。磷酸化糖类对所有研究的细胞毒性机制均有明显抑制作用。这些糖类可能作为一般代谢抑制剂起作用,或者可能激活一个共同信号,对细胞介导的细胞毒性机制产生负调节作用。然而,这些糖类中的大多数(特别是Man-6-P)对NK和ADCC活性的抑制程度比对单核细胞和CTL活性的抑制程度更大。此外,对选定的、特征明确的人及小鼠NK抗性靶细胞的研究强烈表明,这些糖类,特别是Man-6-P,在负责摄取NK裂解因子的受体位点竞争,该受体位点独立于识别结构。